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研究生:吳聞笛
研究生(外文):Wen-Di Wu
論文名稱:利用藥物誘發小鼠大腸炎症及大腸癌之研究
論文名稱(外文):Study of Drug Induced Colitis and Colorectal Cancer in Mice
指導教授:毛嘉洪
指導教授(外文):Chia-hung Mao
學位類別:碩士
校院名稱:國立中興大學
系所名稱:獸醫學系暨研究所
學門:獸醫學門
學類:獸醫學類
論文種類:學術論文
論文出版年:2008
畢業學年度:96
語文別:中文
論文頁數:61
中文關鍵詞:大腸癌炎症DNBSAOMDSS
外文關鍵詞:Colorectal cancerColitisDNBSAOMDSS
相關次數:
  • 被引用被引用:2
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本研究使用C57BL/6JNarl雄性小鼠,由肛門灌入2或3 mg的2,4-Dinitrobenzene sulfonic acid hydrate (DNBS),分別在3天及14天後評估大腸的發炎程度。病理結果顯示在第一次灌藥後3天可見急性大腸炎症反應,並且於某些腸道區段,有大量炎症細胞聚集及腸黏膜壞死的現象。然而在第一次灌藥後14天觀察,炎症反應便已消退,且大腸黏膜皆恢復正常。因此這一動物模式較適合用來研究大腸急性期炎症反應,而不適合做慢性炎症性腸道疾病或進一步誘發大腸癌的探討。文獻指出azoxymethane (AOM)單獨注射或倂用dextran sodium sulfate (DSS)口服可誘發小鼠大腸癌,本研究亦使用C57BL/6JNarl及BKS.Cg-+Leprdb/+Leprdb雄性小鼠,皮下注射AOM 10 mg/kg,每週1次共3次,於40週後始發現aberrant crypt foci (ACF)。另一方面,若選用BALB/cByJNarl雄性小鼠,僅1次腹腔注射相同劑量的AOM,於一週後連續給予7天1% DSS於飲水中,在22週便可觀察到ACF。這些結果顯示配合不同藥物及小鼠品系的使用,可誘發ACF來建立一個良好的動物模式供腸道疾病之研究。
The severities of colonic inflammation were assessed 3 and 14 days after rectum injection of 2,4-Dinitrobenzene sulfonic acid (DNBS) 2 or 3 mg in C57BL/6JNarl male mice. The pathological results showed DNBS produced acute colitis 3 days after first administration with inflammatory cells aggregation and mucosa necrosis, especially in certain sections of colon. However, on day 14, the inflammation had subsided and the mucosa was recovered to normal. Therefore, this animal model is suitable for the study of acute colitis than chronic colitis or further colorectal cancer research. Previous studies showed that injection of azoxymethane (AOM) alone or with oral exposure to dextran sodium sulfate (DSS) could induce mouse colorectal cancer. In this study, C57BL/6JNarl and BKS.Cg-+Leprdb/+Leprdb male mice were treated subcutaneous with AOM 10 mg/kg once a week for 3 weeks. The aberrant crypt foci (ACF) can only be observed after 40 weeks. On the other hand, BALB/cByJNarl mice were given a single intraperitoneal injection of AOM, followed by 1% DSS in drinking water for 7 days, ACF can be observed after 22 weeks. These results indicated that drugs and mouse strains coordination should be considered for ACF induction in the establishment of intestinal disease mouse model.
中文摘要...................................................i
英文摘要..................................................ii
目次.....................................................iii
表次.......................................................v
圖次......................................................vi
第一章、緒言..............................................01
第二章、文獻探討..........................................03
  第一節、胃腸道的生理..................................03
  第二節、大腸癌........................................05
  第三節、炎症與免疫....................................12
  第四節、致腸道癌症及炎症藥物..........................15
  第五節、超音波影像....................................17
  第六節、動物模式......................................20
第三章、材料及方法........................................22
  第一節、實驗動物......................................22
  第二節、藥物配置......................................24
  第三節、實驗設計及流程................................24
  第四節、腸道超音波....................................27
  第五節、樣本分析......................................28
  第六節、統計分析......................................30
第四章、結果..............................................32
  實驗一、以DNBS建立小鼠大腸炎症之動物模式
一、C57BL/6JNarl雄性小鼠以DNBS灌腸後3天大腸組織受損情形...32
二、C57BL/6JNarl雄性小鼠以DNBS灌腸1次或3次後14天大腸組織受損情形......................................................35
三、C57BL/6JNarl雄性小鼠以DNBS灌腸後3 天及14天,大腸組織切片以sirius red染色..........................................37
  實驗二、以AOM建立小鼠大腸癌之動物模式
一、C57BL/6JNarl雄性小鼠皮下注射AOM後33週內之體重變化.....39
二、BKS.Cg-+Leprdb/+Leprdb雄性小鼠皮下注射AOM後33週內之體重變化......................................................39
三、小鼠禁食24小時加上腸道灌水可得較清晰之腸道超音波影像..39
四、C57BL/6JNarl小鼠皮下注射AOM之標準飼料組40週後,大腸組織切片可見ACF...............................................43
五、BKS.Cg-+Leprdb/+Leprdb小鼠皮下注射AOM之標準飼料組56週後,大腸黏膜有腫瘤生成....................................42
  實驗三、以AOM併用DSS建立小鼠炎症相關大腸癌之動物模式
一、BALB/cByJNarl雄性小鼠腹腔注射AOM併用DSS口服,於22週大腸甲基藍染色下可見ACF.......................................46
二、BALB/cByJNarl及C57BL/6JNarl小鼠腹腔注射AOM併用DSS口服,於33週大腸甲基藍染色下皆可見ACF...........................46
第五章、討論..............................................49
參考文獻..................................................55
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